JP3680081B2 - Antibacterial agent for Helicobacter pylori containing chelating agent - Google Patents

Description

[0001]
BACKGROUND OF THE INVENTION
TECHNICAL FIELD The present invention relates to an antibacterial agent for Helicobacter pylori, and more particularly to an antibacterial agent for Helicobacter pylori that contains a chelating agent that has been confirmed to be safe for the human body as an active ingredient.
[0002]
[Prior art]
In recent years, it has been found that bacterial Helicobacter pylori is deeply involved in the development of chronic gastritis and gastric ulcers. In Japan, it is said that about 60 million people, equivalent to half of the total population, are infected with Helicobacter pylori (Food Science 265, 87-99, 2000).
It is possible to cure chronic gastritis and gastric ulcer by removing this bacteria from the stomach by administration of antibiotics, etc., but depending on the patient, it may be difficult to sterilize, and antibiotics are resistant. There are also problems of appearance of bacteria and side effects.
Furthermore, although it is desirable to sterilize not only the affected person but also the infected person, it is economically difficult because the number of subjects becomes enormous.
[0003]
Therefore, there is a need for an antibacterial agent for Helicobacter pylori that is highly safe and can be easily ingested.
Ethylenediaminetetraacetic acid (hereinafter sometimes abbreviated as EDTA) has a chelating action on various metal ions, and is known as an enzyme reaction inhibitor that requires metal ions. In addition, EDTA and its metal salts are recognized as food additives in many countries because they have a food color stabilizing effect.
[0004]
Thus, safety evaluations such as EDTA have already been established, and the daily intake tolerance (ADI) as a food additive is 2.5 mg / kg body weight (FAO / WHO: Codex Alimentarius Commission, List of additives evaluated for their safety in use in food. CAC / FAL 1-1973, 1973). In the United States, it is recognized that disodium EDTA is added to foods in a concentration range of 36 to 500 ppm (Code of Federal Regulations, Title 21: Food and drugs, US Government Printing Office, 1988).
[0005]
[Problems to be solved by the invention]
An object of the present invention is to provide an antibacterial agent having an action of inhibiting the growth of Helicobacter pylori involved in the development of chronic gastritis and gastric ulcer and containing a highly safe substance as an active ingredient.
[0006]
[Means for Solving the Problems]
In order to solve the above problems, the present inventors searched for antibacterial substances for Helicobacter pylori among substances recognized as food additives. As a result, EDTA, which is a kind of chelating agent, and metal salts thereof Was found to have an action of inhibiting the growth of Helicobacter pylori, and the present invention was completed based on such findings.
[0007]
That is, the present invention relates to an antibacterial agent for Helicobacter pylori characterized by containing 0.1 to 0.5 mM of ethylenediaminetetraacetic acid iron ( III) -sodium as an active ingredient .
[0008]
DETAILED DESCRIPTION OF THE INVENTION
In the present invention, a substance selected from metal salts of EDTA is used as an active ingredient of an antibacterial agent for Helicobacter pylori.
The metal salt of EDTA is not particularly limited as long as it has a desired antibacterial action, and ethylenediaminetetraacetic acid iron ( III) -sodium is preferable.
[0009]
The antibacterial agent according to the present invention can be in various forms, for example , using a metal salt of EDTA alone, and using it with an appropriate auxiliary agent (for example, excipient, bulking agent, sweetener, etc.) as necessary. And can be made into dosage forms such as powders, granules, liquids, capsules and the like. The metal salt of EDTA can also be used by adding to various foods. The antibacterial agent according to the present invention is usually administered orally.
[0010]
Regarding the dose of the metal salt of EDTA, the ADI of EDTA is 2.5 mg / kg body weight, and these effective amounts for inhibiting the growth of Helicobacter pylori, as well as the volume of the human stomach (about 1.5L) etc. may be taken into consideration.
In order to inhibit the growth of Helicobacter pylori in the stomach, a metal salt of EDTA may be administered as an EDTA purified product per adult per day, about 10 to 500 mg, preferably about 10 to 150 mg. . In the case of iron (III) -sodium ethylenediaminetetraacetate, it is appropriate to administer about 60 to 300 mg, preferably about 60 to 150 mg per day per adult. Excessive administration may cause side effects. In addition, administration of EDTA etc. may be performed for the whole quantity at once, or may be performed in several times.
[0011]
The antibacterial agent of the present invention may be used in combination with a proton pump inhibitor such as omeprazole or an anti-ulcer agent such as a bismuth preparation.
[0012]
【Example】
Hereinafter, the present invention will be described in detail with reference to examples, but the present invention is not limited thereto.
[0013]
Example 1
Helicobacter pylori (ATCC 43504 strain, purchased from American Type Culture Collection) was cultured using a microtiter plate. That is, 3% tryptic soy broth (Difco), 10% tissue culture calf serum (Wako Pure Chemical), and various concentrations of ethylenediaminetetraacetate (so-called Wako Pure Chemical) adjusted to pH 8.0 or ethylenediamine Dispense 0.1 mL of a medium composed of iron (III) tetraacetate-sodium (Donjin Chemical) into a 96-well microplate, inoculate with Helicobacter pylori, and place in a 2.5-liter sealed container. Furthermore, an anero-pack helicopter (manufactured by Mitsubishi Gas Chemical), which is an oxygen absorption / carbon dioxide generator, was added and cultured at 37 ° C. for 5 days under anaerobic conditions.
The growth of Helicobacter pylori was measured in a microtiter plate reader using a 540 nm or 595 nm filter. In addition, the culture medium which does not contain EDTA was used for the control of absorbance measurement. The results are shown in FIG. 1 and FIG. The figure shows the growth of Helicobacter pylori with turbidity in response to changes in the concentration of the active ingredient EDTA, etc., and shows the ratio to the turbidity when Helicobacter pylori was grown in a control medium. .
[0014]
FIG. 1 shows that the growth of Helicobacter pylori ATCC 43504 is inhibited by 0.025 to 1 mM disodium ethylenediaminetetraacetate. Moreover, it turns out that the proliferation of the said H. pylori is inhibited also by 0.1-0.5 mM ethylenediaminetetraacetic acid iron (III) -sodium from FIG.
[0015]
By the way, 0.025 to 1 mM of disodium ethylenediaminetetraacetate (molecular weight 372) is converted to 9.3 to 372 mg / L, and has an upper limit concentration of addition of 500 ppm or less to foods recognized in the United States.
Moreover, since the volume of the human stomach is said to be about 1.5 L, if ethylenediaminetetraacetate disodium is ingested 14 to 558 mg (11 to 438 mg as EDTA), the growth of Helicobacter pylori is inhibited. be able to.
On the other hand, in the case of ethylenediaminetetraacetic acid iron (III) -sodium (molecular weight 421.1), the intake of 63 to 316 mg can inhibit the growth of Helicobacter pylori.
[0016]
【The invention's effect】
The present invention provides an antibacterial agent for Helicobacter pylori that is recognized as a food additive in many countries and contains a highly safe metal salt of EDTA as an active ingredient.
More that the antimicrobial agent administered either alone or in a suitable aid, or to feed be contained in foods, it is possible to effectively inhibit the growth of Helicobacter pylori bacteria present in the human digestive system. Therefore, according to the present invention, it is possible to effectively prevent and treat gastrointestinal disorders that have been reported to involve H. pylori.
[Brief description of the drawings]
FIG. 1 is a graph showing the growth rate of Helicobacter pylori in the presence of disodium ethylenediaminetetraacetate at various concentrations.
FIG. 2 is a graph showing the growth rate of Helicobacter pylori in the presence of various concentrations of ethylenediaminetetraacetate (III) -sodium.

Claims (1)

An antibacterial agent for Helicobacter pylori characterized by containing only 0.1 to 0.5 mM of ethylenediaminetetraacetic acid iron ( III) -sodium as an active ingredient .

Images